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Statin therapy (atorvastatin 80 mg or simvastatin 40 mg) should be given to all patients following an ischaemic stroke or TIA irrespective of cholesterol level

Anticoagulation with warfarin should be given to all patients in atrial fibrillation following ischaemic stroke and TIA unless a significant contraindication exists—age and falls should not prevent anticoagulation use

Following stroke (both ischaemic and haemorrhagic), offer antihypertensive therapy with an ACE inhibitor and thiazide diuretic to control blood pressure

Stroke is the third commonest cause of death in the UK, where, each year, 150,000 people will have a stroke.1 Of these, 111,000 are first strokes.2 The prevalence of stroke in people aged over 75 years rose from 9% in 1994 to 13% in 2006.2 Immediate mortality is high, with around 20% of patients dying within 30 days following stroke.3 Around 53,000 people die each year in the UK from stroke with 5% of these events occurring in those under the age of 75 years.2

Burden of stroke

Although stroke mortality is declining overall, there remain significant disparities in mortality rates within the UK, which are 50% higher in Scotland than in London. The rate of premature mortality from stroke is three times higher in areas of greatest social deprivation compared with the least deprived areas.1

In terms of NHS resources, patients with stroke occupy one in five acute hospital beds and one in four long-term beds. Stroke remains the commonest cause of disability and there are over 300,000 stroke survivors in the UK with moderate to severe disability. The total economic cost attributed to stroke in the UK for 2006/07 was £4.5 billion.1,2

Stroke is, therefore, a disease that has a significant impact on affected individuals, their families and carers, and is relevant to healthcare professionals in all disciplines. Guidelines for stroke management have greatly influenced modern stroke care, which has moved from a rehabilitation-focused specialty to a much more acute discipline. The Scottish Intercollegiate Guidelines Network (SIGN) guideline 108, Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention, launched in December 2008, has raised the profile of acute stroke care and provides many recommendations for healthcare professionals in primary and secondary care.4

Prompt transfer for hospital assessment

The key message is that stroke and transient ischaemic attack (TIA) are acute medical emergencies and need to be treated as such. Public information campaigns have focused on the FAST (face, arm, speech, time) mnemonic—which is simple and easy for laypersons and healthcare professionals to apply—to improve the rapid detection of stroke symptoms and signs allowing urgent referral to acute medical services.5,6

From the onset of the first stroke symptom, timing is critical: ‘time is brain’; and early assessment, diagnosis, and hospital treatment of patients with a suspected stroke reduce both morbidity and mortality. To facilitate rapid transfer of patients with suspected stroke to specialist assessment, emergency medical services need to be contacted immediately via the 999 ambulance service. Protocols should be in place to ensure that patients are taken to an acute stroke centre where rapid hospital triage to a specialist stroke assessment and urgent brain imaging can be performed. General practitioners should not delay admission when an acute stroke is suspected.5

Healthcare professionals who live and work in geographically remote and rural areas of the UK, particularly in Scotland, face significant challenges as there may be no local direct access to a specialist stroke service and distances make rapid transfer to an acute stroke centre unfeasible. In these situations, telemedicine consultations with a remote stroke specialist can facilitate the safe administration of acute stroke treatments in appropriate patients.4,7

Treatment

Treatment of acute stroke and TIA is aimed both at treating the acute event and secondary prevention. In acute ischaemic stroke the only two treatments of proven benefit in the hyperacute phase are thrombolysis with recombinant tissue plasminogen activator (rt-PA) and aspirin. However if the individual is a candidate for thrombolysis, then aspirin should be withheld for 24 hours following this treatment to reduce the risk of haemorrhagic complications.4 As with cardiovascular disease many treatments in combination—aimed at controlling vascular risk factors—are of benefit in secondary prevention.

Thrombolysis treatment with intravenous rt-PA (alteplase) has been shown to be safe and of benefit in acute ischaemic stroke if administered rapidly following stroke onset.8 This treatment is now available in most acute hospitals in the UK. Recent evidence has extended the time window for treatment to 4.5 hours from symptom onset as recommended by SIGN,4,9 but the benefits are greatest the sooner altepase is administered.10 All patients with suspected stroke should be referred urgently to an acute stroke centre capable of administering thrombolytic therapy if clinically indicated.4

For patients who have had a TIA or minor stroke, the risk of experiencing a recurrent stroke within the first week following the initial event is up to 10%.11 The ABCD2 score can be used to identify individuals in high-risk groups in order to target rapid investigation and treatment (see Table 1).12,13 The 90-day recurrent stroke risk is reduced by 80% from 10.3% to 2.1% if patients with TIA are promptly seen in neurovascular clinics for treatment.11 This includes initiation of dual antiplatelet, statin, and antihypertensive treatment, and anticoagulation therapy for patients in atrial fibrillation (AF), carotid imaging, and carotid endarterectomy if appropriate.11

Antiplatelet therapy
Once neuroimaging has excluded an intracerebral haemorrhage, antiplatelet therapy should be initiated as soon as possible following TIA and stroke.4 Early administration of aspirin (300 mg) within 48 hours of stroke reduces death and disability, recurrent stroke, and increases the chance of a full recovery.4,14 This dose should be continued for 14 days and then reduced to 75 mg maintenance.4 The addition of modified-release dipyridamole 200 mg twice daily maximises the reduction in risk of further stroke and should also be prescribed.4,15 Early versus delayed (after 7 days from onset) introduction of dipyridamole showed no difference in outcome.16 A common side-effect of dipyridamole is headache;4 this affects around one third of patients and leads to intolerance, but dose titration may reduce this problem.

Clopidogrel 75 mg monotherapy can be used if the patient is allergic to aspirin or intolerant to dipyridamole and has been demonstrated to be non-inferior to the combination of aspirin and dipyridamole in one trial.17 The routine use of aspirin and clopidogrel combination therapy is not recommended following stroke or TIA. Emerging evidence suggests that aspirin and clopidogrel in combination for high-risk patients following TIA may be beneficial for short-term treatment but this remains to be formally evaluated in randomised controlled trials.11,18,19

Statin therapy
Statin therapy should be given to all patients with ischaemic stroke and TIA irrespective of cholesterol level.4 Consideration should be given to the use of atorvastatin 80 mg as the first-choice therapy for reducing the risk of subsequent cerebrovascular disease following stroke, with simvastatin 40 mg also reducing the risk of major vascular events.20,21 Due to the small hazard of intracerebral haemorrhage with statin treatment they should not be used routinely following a primary intracerebral haemorrhage.22

Anticoagulation therapy
Anticoagulation therapy with warfarin should be offered to all patients with ischaemic stroke or TIA who have persistent or paroxysmal AF, where no contraindication exists, aiming for a target international normalised ratio of 2.0–3.0.4 Warfarin treatment has been shown to reduce annual stroke risk by 68% compared with a reduction of 20% in people receiving aspirin.23 There is no evidence to support the addition of aspirin to warfarin therapy. Despite clear evidence of benefit, warfarin remains underused in patients in AF particularly in the elderly who are at the highest risk of stroke. A community study of elderly patients aged over 75 years in the UK (BAFTA: Birmingham Atrial Fibrillation Treatment of the Aged Study) showed that warfarin can be used safely in this age group with similar rates of haemorrhagic complications in both aspirin and warfarin treated groups (rate of extracranial haemorrhage was 1.4% on warfarin and 1.6% on aspirin).24

The perceived risk of falls in patients on warfarin therapy is likely to be overestimated. Elderly patients who fall have a mean of 1.81 falls per year; taking into account the risks of subdural haemorrhage, an individual would need to fall around 295 times in 1 year for warfarin not to be the optimal treatment for AF.25

A novel direct thrombin inhibitor, dabigatran, has recently been shown to be more effective than warfarin in prevention of thrombotic events (stroke or systemic embolism) in AF.26 Additional benefits of this agent are that it has predictable dosing, is less susceptible to drug and dietary interactions, and does not require anticoagulation monitoring. This evidence was not available for consideration in SIGN 108 and the cost effectiveness of this treatment needs to be confirmed before recommendations can be made for routine clinical use.

Antihypertensive medication
Following TIA or stroke (both ischaemic and haemorrhagic), all patients will benefit from blood pressure (BP) lowering even if normotensive to a BP of 125/75 mmHg. Treat patients with an angiotensin-converting enzyme (ACE) inhibitor (such as perindopril) and a thiazide diuretic (such as indapamide) aiming for a target BP of <140/85 mmHg or <130/80 mmHg if diabetes is also present.4,27

Carotid assessment and treatment
All patients with non-disabling acute stroke syndrome/TIA in the carotid territory who are potential candidates for carotid endarterectomy should have carotid imaging to identify individuals with stenosis of the internal carotid artery (ICA). Initial carotid imaging will usually be performed with duplex ultrasound but computed tomography angiography, magnetic resonance angiography, or contrast-enhanced magnetic resonance angiography may also be used. Carotid endarterectomy should be offered to male patients with an ICA stenosis of 50%–99% and to female patients with an ICA stenosis of 70%–99%.4 There is no upper age limit for surgery if the patient is considered fit for intervention. The benefits of surgery are greatest within the first 2 weeks with only five patients needing treatment to prevent one stroke however if surgery occurs more than 12 weeks after the event then 125 patients need treatment to prevent one stroke.28

Treatment of haemorrhagic stroke
Haemorrhagic stroke accounts for around 10% of strokes;29 however, despite extensive research, no routine therapies have been proven to be of benefit in patients with this type of stroke. Neurosurgical clot removal as a treatment option has proven disappointing, but further trials are ongoing.30 Although haemostatic treatment with recombinant factor VIIa reduced the growth of intracerebral haematomas, there was no improvement in survival or functional outcome at 90 days and an increase in arterial thromboembolic events was noted.31

Conclusion

The main challenges for GPs involved in stroke care are to encourage the education of their patients, particularly those at high vascular risk, in the recognition of stroke symptoms, and to urge them to seek help rapidly from the emergency medical services if symptoms occur. For individuals with TIA, the rapid initiation of secondary prevention with antiplatelet, statin, and antihypertensive therapy will reduce the risk of further stroke pending urgent assessment at a neurovascular clinic.

Patients who are known to have experienced cerebrovascular disease should be on the practice register and have the following documented: blood pressure, cholesterol level, smoking status, and review of their secondary prevention. Putting the SIGN guideline into practice will further reduce the burden of stroke disease, which is devastating for both the patient and their family/carers.

The SIGN guideline applies to Scotland where there is no PBC whereas in England there is a National Stroke Strategy and NICE guidance

Emergency (999) referral should take place for people with likely stroke symptoms and within 24 hours for those with TIA and an ABCD2 score of 4 or more

The use of FAST and ABCD2 tools by emergency and primary care staff is recommended—this can be defined in a care pathway

Commissioners should agree a care pathway for secondary stroke prevention; they should be mindful that blood pressure targets are lower than that for the quality and outcomes framework

The SIGN guideline recommends consideration of the use of high-dose atorvastatin (80 mg) post stroke, but the NICE guideline does not!

Heart Protection Study Collaborative Group. Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20,536 people with cerebrovascular disease or other high-risk conditions. Lancet 2004; 363 (9411): 757–767.

Vergouwen M, de Haan R, Vermeulen M et al.Statin treatment and the occurrence of haemorrhagic stroke in patients with a history of cerebrovascular disease. Stroke 2008; 39 (2): 497–502.